PRINCIPAL INVESTIGATORS

Jean Lud Cadet, M.D., Senior Investigator

Chief, Molecular Neuropsychiatry Research Branch
Associate Director for Diversity and Outreach

M.D. - Columbia University College of Physicians and Surgeons

Residencies
- Department of Psychiatry at Columbia University College of Physicians and Surgeons
- Department of Neurology at Mount Sinai Medical Center in NYC

Post-Doctoral Fellowship - Neuropsychiatry Branch, NIMH

RESEARCH INTERESTS

Research in our section focuses on studies the molecular and cellular mechanisms of psychostimulant addiction and toxicity. Dr. Cadet’s group has provided recent evidence that methamphetamine (METH) self-administration is accompanied with markers of toxicity in striatal dopaminergic systems. These results are consistent with the idea that catecholamines, especially, dopamine can activate neurodegenerative processes in the mammalian brain. We have also shown recently that METH preconditioning protects against METH toxicity. This occurs by upregulation of neurotrophic factors such as BDNF and/or downregulation of glutamatergic systems. Preliminary studies have shown that these changes are secondary to epigenetic modifications that include histone hypoacetylation and DNA methylation. The laboratory is thus pursuing investigations to further identify epigenetic markers that are involved in METH self-administration and METH preconditioning.

Selected Publications:

1. Jayanthi, S., Deng, X., Ladenheim, B., McCoy, M.T., Cluster, A., Cai, N.S., Cadet, J.L. Calcineurin/NFAT-induced up-regulation of the Fas ligand/Fas death pathway is involved in methamphetamine-induced neuronal apoptosis. Proc Natl Acad Sci. 2005; 102: 868-873.

2. Krasnova, I.N., Ladenheim, B., Cadet, J.L. Amphetamine induces apoptosis of medium spiny striatal projection neurons via the mitochondria-dependent pathway. FASEB J. 2005; 19: 851-853.

3. Thiriet N., Deng, X., Solinas, M., Ladenheim, B., Curtis, W., Goldberg, S.B., Pa;miter, R.D., Cadet, J.L. Neuropeptide Y protects against methamphetamine-induced neuronal apoptosis in the mouse striatum. J Neuroscience 2005; 25: 5273-5279.

4. Krasnova I.N., Li S.M., Wood W.H., McCoy M.T., Prabbu V.V, Becker K.G., Katz J.L., Cadet J.L. Transcriptional responses to reinforcing effects of cocaine in the rat hippocampus and cortex. Genes Brain Behav. 2008; 7: 193-202.

5. Sekine Y., Ouchi Y., Sugihara G., Takei N., Yoshikawa E., Nakamura K., Iwata Y., Tsuchiya K.J., Suda S., Suzuki K., Kawai M., Takebayashi K., Yamamoto S., Matsuzaki H., Ueki T., Mori N., Gold M.S., Cadet J.L. Methamphetamine causes microglial activation in the brains of human abusers. J Neurosci. 2008; 28: 5756-5761.

6. Cadet JL, Jayanthi S, McCoy MT, Beauvais G, Cai NS. Dopamine D1 receptors, regulation of gene expression in the brain, and neurodegeneration. CNS Neurol Disord Drug Targets 2010; 9: 526-538.

7. Krasnova IN, Justinova Z, Ladenheim B, Jayanthi S, McCoy MT, Barnes C, Warner JE, Goldberg SR, Cadet JL. Methamphetamine self-administration is associated with persistent biochemical alterations in striatal and cortical dopaminergic terminals in the rat. PLoS One 2010, 5: e8790.

8. Krasnova IN, Ladenheim B, Hodges AB, Volkow ND, Cadet JL. Chronic methamphetamine administration causes differential regulation of transcription factors in the rat midbrain. PLoS One 2011; 6: e19179.

9. Beauvais G, Atwell K, Jayanthi S, Ladenheim B, Cadet JL. Involvement of dopamine receptors in binge methamphetamine-induced activation of endoplasmic reticulum and mitochondrial stress pathways. PLoS One 2011; 6: e28946.

10. Martin TA, Jayanthi S, McCoy MT, Brannock C, Ladenheim B, Garrett T, Lehrmann E, Becker KG, Cadet JL. Methamphetamine causes differential alterations in gene expression and patterns of histone acetylation/hypoacetylation in the rat nucleus accumbens. PLoS One 2012; 7: e34236.